PIPELINE REPORT 2015 - media.mmm-online.commedia.mmm-online.com/documents/97/41r1_mmm_dec14_24005.pdf · Results of Merck’s IMPROVE-IT ... THE PIPELINE REPORT 2015 These 16 sprouts,

Autoimmune 37

Cardiology 38

Infectious Disease 39

Oncology 40

Respiratory 41

Other 42

When the dust settles on another year and analysts take stock, 2014 is set to go down as one of the most interesting in terms of R&D productivity—not just how many drugs

the FDA sanctioned, but how valuable they prove commercially. Thank Gilead’s Sovaldi for that. The drug for hepatitis C virus

became a blockbuster in record time while raising cure rates, and its recently approved hep. C cousin Harvoni is poised to do well as it sheds ribavirin and interferon from treatment regimens. AbbVie has another interferon- and ribavirin-free regimen waiting in the wings.

The hep. C progress is evidence of one type of industry innovation: “the good old-fashioned wizardry of attacking big problems with big solutions,” says Mike Luby, founder, president and CEO of BioPharma Alliance. Others are on the horizon. In the oncology pipeline are PD-1/L1 inhibitors from Bristol-Myers Squibb and AstraZeneca. In neurology, firms are testing BACE inhibitors against Alzheimer’s, and in respiratory, investigational drugs from GlaxoSmithKline, Roche and Novartis could lower the steroid burden for patients with severe asthma and COPD.

A second kind of advance has been evolutionary: finding solutions for patients, physicians and payers in what seemed satisfied markets. That’s where products and new classes of drugs have led to advances in therapeutic categories, some thought to already be well-served.

Luby points to cardiology as one such category: ACE inhibitors like Vasotec have been mainstays of treating heart failure. New research shows that by switching patients from an ACE inhibitor to Novartis’s LCZ696, survival is prolonged.

In the cholesterol area, statins were once reserved for more severe cases. Now, the PCSK9 inhibitors from Amgen and Sanofi/Regeneron may be approved for hard-to-treat patients—and could move into a less and less reserved position. Results of Merck’s IMPROVE-IT trial, released last month, “support the notion that the goalposts will move over time, as the science shows greater benefits,” says Luby.

It’s hard to call psoriasis a satisfied market, although anti-TNFs Enbrel and Humira changed the treatment paradigm, as did IL-12 drug Stelara. Now, Amgen/AstraZeneca, Eli Lilly and Novartis are working on IL-17 drugs that could raise the bar further in psoriasis.

And in diabetes, the GLP-1 and SGLT2 drugs gave doctors new ways to treat this epidemic. Once-weekly versions of some of these same products have altered the patient experience.

In addition to the autoimmune, cardiology, infectious disease, oncol-ogy and respiratory sectors, the following pages highlight promising orphan therapies, and outline late-stagers in the metabolic, neurology and women’s health areas, and some in other stages. (At press time, Sanofi’s Lemtrada received approval for MS, but had yet to launch.)

Profiled agents are based on consultation with inThought, Adis R&D Insight, GfK HealthCare and other experts. Original analysis reflects the latest data sets (as of press time), and is complemented by revenue forecasts, lists of other key products and, where available, the estimated month of launch, plus a percentage giving an indication of the likelihood of success (anything over 50% stands a good chance).

THERAPEUTIC CATEGORIES

DREAM DRUGS

36 MM&M x DECEMBER 2014 x mmm-online.com

THE PIPELINE REPORT 2015

These 16 sprouts, from a field of 156, are looking up. With more nurturing, their buds could blossom. Marc Iskowitz reports

PH

OTO

: GE

TT

YIM

AG

ES

PIPELINE 2014

PRODUCTS GENERATING BUZZ

Brodalumab Amgen/AstraZenecaIndication: Plaque psoriasis/psoriatic arthritis (Ph. III)What the clinical trials found: In a Phase-III trial vs. Janssen’s Stelara (AMAGINE-3), 36% of brodalumab 210mg patients with moderate-to-severe plaque psoriasis vs. 18.5% of the Stelara group achieved PASI 100. No clinically significant safety issues seen.Credit Suisse Success Probability and inThought Comment: 50%. It looks like Novartis’s secukinumab could be the first of the three IL-17 receptors to be approved. What sets brodalumab apart is Amgen’s clinical trial program, with head-to-head trials vs. Stelara—that should give reps a talking point. Expected launch: 2016 (Source: Credit Suisse) Credit Suisse revenue forecast: $371 million in global annual pso-riasis sales by 2020 What the physicians are saying: There is limited biologic usage in psoriasis due to the conservative nature of dermatologists and under-estimation of severity. Almost a fifth of patients with body surface area of over 10% are classified as mild. However, opportunity for another biologic exists in this market given lack of control with cur-rent treatment; about three-fifths of consulting patients are unstable/deteriorating (GfK Disease Atlas 2013 USA). Safety results will trump MOA, although it is recognized that the IL-17 pathway plays a central role in inducing and promoting inflammatory disease pro-cesses. —Alison Rose, therapy lead–immunology, Disease Atlas, GfK

Lemtrada (alemtuzumab) SanofiIndication: Multiple sclerosis (Registered)What the clinical trials found: After FDA rejected Lemtrada last December, an extension study showed its effects were stable over four years with no new risks. Lemtrada showed effectiveness in relapse reduction and a slowing of physical disability superior to Merck/EMD Serono’s Rebif (CARE-MS I, CARE-MS II), and patients were more likely to stay relapse-free for two years. Serious AEs included ITP.Credit Suisse Success Probability and inThought Comment: 100%. Sanofi has to find patients willing to take the risk. Also, they found the drug works much better early in disease. So it seems patients must decide early on—take Lemtrada, or take other options and completely forego Lemtrada. That’s a hard choice for someone in their 30s who was just diagnosed. Expected launch: 2015 (Source: Credit Suisse)Credit Suisse revenue forecast: $899 million in global annual sales by 2020What the physicians are saying: Lemtrada is approved in the EU, Canada, Australia and Mexico, and after a delay was approved in the US (at press time). It’s still on neurologists’ minds: 50% were aware of it on an unaided basis, 85% aided. Neuros most often mention dosing (once- or twice-yearly infusion), very strong efficacy as well as potentially dangerous SEs. Over two-thirds of those aware of the drug see it as an option for later lines of therapy. Neurologists will have patients willing to take the risk, having failed on other treat-

AutoimmuneDaclizumab AbbVie/Biogen IdecMS (Ph.III)

Adalimumab biosimilar AmgenRA (Ph.III)

Romosozumab AmgenOsteoporosis (Ph.III)

Ocrelizumab Biogen Idec/RocheMS (Ph.III)

Remsima (infliximab biosim) CelltrionAnkylosing spond./CD/RA (Ph.III)

Etanercept biosimilar Daiichi SankyoPlaque psosiasis/RA (Ph.III)

Baracitinib Eli LillyRA (Ph.III)

Ixekizumab Eli LillyPlaque psoriasis/psoriatic arth. (Ph.III)

Infliximab biosimilar EpirusRA (Ph.III)

Ertolizumab GenentechUlcerative colitis (Ph.III)

Sirukumab JanssenRA (Ph.III)

Odanacatib MerckOsteoporosis (Ph.III)

Tildrukizumab MerckPlaque psoriasis (Ph.III)

Secukinumab NovartisPlaque psoriasis (Pre-reg.)

Siponimod NovartisMS (Ph.III)

Fablyn (lasofoxifene) PfizerOsteoporosis (Pre-reg.)

Sarilumab RegeneronRA (Ph.III)

Viviant PfizerOsteoporosis (Pre-reg.)

Laquinimod TevaMS (Ph.III)

OTHER KEY PRODUCTS IN THE PIPELINE

mmm-online.com x DECEMBER 2014 x MM&M 37

ments, but for Lemtrada to excel, it must be more than a last-resort option. —Paul Wojciak, research director, health, GfK

Mongersen (GED-0301) CelgeneIndication: Crohn’s disease (Ph. II/III)What the clinical trials found: Ph. II evidence (showcased at UEGW) showed clinical remission and clinical response greater than placebo, with similar AE profile in steroid-dependent/steroid-resistant patients.Credit Suisse Success Probability and inThought Comment: 70%. Mongersen won’t be approved for three years, but we don’t have any oral drugs for ulcerative colitis or Crohn’s the way we do for RA and—because of Celgene—for psoriasis (Otezla). That would be welcome for those patients. Expected launch: 2019 (Source: Credit Suisse)Credit Suisse revenue forecast: $1.1B in global annual sales by 2020What the physicians are saying: Mongersen is a novel therapy with a unique MOA; first-in-class oral antisense therapy. It is assumed Ph.III head-to-head trial will be vs. AbbVie’s Humira. Physicians will still compare Mongersen with available TNFs, plus other Ph.II/III com-petition (e.g. JAKs). To get uptake of oral vs. s/c or IV, Celgene must promote patient convenience and financial gain due to no product wastage/dose escalation. The market must be conditioned to break TNF cycling. —Alison Rose, therapy lead–immunology, Disease Atlas, GfK

PIPELINE 2015 UEROSTO COMMODO ODIONUL


Acanetrapib MerckIndication: Atherosclerosis/hypercholesterolemia/hyperlipopro-teinemia (Ph.III)What the clinical trials found: At 24 weeks, anacetrapib decreased LDL-C by 40% and increased HDL-C by 138% in patients already treated with a statin and at guideline-recommended LDL-C goal (DEFINE). CV events occurred in 2% of patients given anacetrapib vs. 2.6% given placebo. Credit Suisse Success Probability and Comment: 60%. The clinical trial results give researchers confidence to start larger cardiovascular clinical outcomes trials, which is important because an early CETP inhibitor, torcetrapib, was found to cause an excess of deaths and cardiovascular events. Expected launch: 2017 (Source: Credit Suisse) Credit Suisse revenue forecast: $2.1 billion in global sales by 2020What the physicians are saying: The drug will have to demonstrate that it doesn’t have off-target toxicities. These have plagued other drugs that, ultimately, never made it to the market. Based off its strong clinical performance, in an area that is notoriously difficult to address—HDL—it will likely be a major blockbuster if it can navigate the path to market. Another hurdle will be in proving that the drug reduces CV events. This has largely been taken true but, as we’ve seen with Zetia, nothing is certain until there’s hard data to prove it. —Alex Bastian, VP, GfK Market Access (health)

Evolocumab/AMG-145 AmgenIndication: Hypercholesterolaemia/hyperlipoproteinaemia (Pre-reg.)What the clinical trials found: Mean LDL-C reduction of 66%-75% (week 10) and 63%-75% (week 12) from baseline vs. placebo group, and a reduction of 38%-45% and 44% vs. ezetimibe-treated groups (LAPLACE-2), as well as statistically significant reductions in LDL-C vs. placebo in patients with HeFH and HoFH (TESLA and RUTHERFORD-2). It’s considered safe and tolerable.Credit Suisse Success Probability: 65%. Expected launch: 2016 (Source: Credit Suisse) Credit Suisse revenue forecast: $927 million in global annual sales by 2020What the analysts are saying: Three major factors will impact success in market: 1) long-term data on the potential to reduce CV events; 2) the right market-access strategy that makes prudent trade-offs in access to patients and price, important in a market dominated by cheap statins; and 3) speed. Sanofi and Regeneron made things interesting over the summer when they paid $67.5 million for an FDA voucher to cut rival PCSK9 inhibitor alirocumab’s review time down from 10 months to six. Amgen’s lawsuit claims that Sanofi and Regeneron stepped on its IP. The three patents in question apply to antibodies to PCSK9, including Amgen’s own evolocumab, and the lawsuit seeks to prevent the manufacture, use and sale of Sanofi and Regeneron’s similar alirocumab. —Alex Bastian, VP, GfK Market Access (health)

CardiologyAzimilide ActavisVentricular arrhythmias (Ph.III)

Ivabradine AmgenCHF (Pre-reg.)

Roxadustat AstraZenecaAnemia in CKD (Ph.III)

Cangrelor AstraZenecaCAD (Pre-reg.)

Betrixaban Daiichi SankyoThromboembolism (Ph.III)

Edoxaban Daiichi SankyoEmbolism (Pre-reg.)

Evacetrapib Eli LillyCV disorders (Ph.III)

Ranolazine GileadIncomplete revascularization (Ph.III)

Darapladib GSKAtherosclerosis (Ph.III)

Desmoteplase Lundbeck A/SStroke (Ph.III)

Cordaptive MerckAtherosclerosis (Ph.III)

Pradigastat/LCQ908 NovartisHyperlipoproteinemia (Ph.III)

Serelaxin NovartisAHF (Pre-reg.)

Bococizumab/RN-316 PfizerHypercholesterolemia (Ph.III)

Andexanet alfa PortolaFXa inhibitor antidote (Ph.III)

Fostamatinib RigelITP (Ph.III)

CEP-41750 TevaCHF (Ph.III)

Perindopril/amlodipine XOMAHypertension (Pre-reg.)



LCZ696 (Diovan + AHU377) NovartisIndication: Heart failure/hypertension (Ph. III)What the clinical trials found: Patients receiving LCZ696 had a 20% reduction in the risk of cardiovascular mortality, a 21% reduction in hospitalizations due to HF and a 16% reduction in the risk of all-cause mortality vs. the enalapril cohort (PARADIGM-HF). There was marginal increase in nonserious angioedema.Credit Suisse Success Probability: 75%. Expected launch: 2015 (Source: Credit Suisse) Credit Suisse revenue forecast: $4.2 billion in global annual sales by 2020What the physicians are saying: Novartis will be entering a cardio-vascular marketplace where price-sensitivity has become an increas-ingly important issue, a consideration that will undoubtedly play a role in the company’s price-setting. A month’s supply of enalapril costs roughly $4, whereas analysts predict LCZ696 will be priced between $7 and $8 per day (in the US). The drug, however, has demonstrated a compelling clinical profile. It met all of its major endpoints in all the subgroups without raising any sort of a safety signal. Because of this, both market access and pricing strategy will play a key role in the uptake of LCZ696—a potential block-buster in the making.The way that guidelines incorporate this into the paradigm is also going to be critical. —Alex Bastian, VP, GfK Market Access (health)




Daclatasvir Bristol-Myers SquibbIndication: Hepatitis C (Pre-reg.)What the clinical trials found: Effective when used in combina-tion, including with BMS’s own asunaprevir. However, its efficacy appears to be greatest in studies where it was used with Gilead’s Sovaldi, achieving cure rates above 90% including among patients with advanced liver disease, GT-3 and those who had previously failed on a protease inhibitor.Credit Suisse Success Probability: 80%. Expected launch: 2016 (Source: Credit Suisse)Credit Suisse revenue forecast: $1.4 billion in global annual sales by 2020What the analysts are saying: Benefits include shorter treatment duration (12 or 24 weeks) compared to 48 weeks of treatment with INF- and RBV-based regimens, and it’s been part of an all-oral, INF-free regimen that achieved 100% cure rates. However, given that daclatasvir appears to work best in combination with Solvaldi, the primary competition may in fact be with Johnson & Johnson’s Olysio (simeprevir), as it is also often used in combination with the same Gilead product. The “better” combination may be determined by patient subtypes, side effects/tolerability or convenience. —Michael D’Aust Garcia, SVP, GfK Health

Veruprevir (ABT-450)/r + ombitasvir (-267) + dasabuvir (-333) AbbVieIndication: Hepatitis C (Pre-reg.)What the clinical trials found: SVR12 rates of 99.5% and 99.0% in GT-1b HCV patients in Ph.III, used with or without RBV, respec-tively (PEARL-III). SVR12 rates were 97% and 90% among GT-1a HCV patients (PEARL-IV). Bernstein Research revenue forecast: $2.3 billion in global annual sales by 2020What the analysts are saying: Physicians are excited, particularly by the AbbVie regimen’s extremely low discontinuation rates. Given that GT1 is the most common HCV genotype, physicians acknowledge that there is a high unmet need within these patients for better effi-cacy, safety and oral therapy. But it faces extremely stiff competition, namely from Gilead, which recently introduced Sovaldi (sofosbuvir) and Harvoni (ledipasvir + sofosbuvir), and continues to test other new compounds and various HCV genotypes. Others who are working on compounds in this space include BMS (see above) and Merck, although its grazoprevir + elbasvir combo recently fell short of efficacy goals. Given that all of the new agents appear to contribute to high cure rates, it appears that the fight will likely be won with the better side effects/tolerability, convenience factors (fewer pills) or even potentially on price (Gilead’s current pricing is described as “astronomical”). —Michael D’Aust Garcia, SVP, GfK Health

Infectious Disease

Atazanavir+cobicistat BMS/GileadHIV-1 inf. (Pre-reg.)

Brincidofovir ChimerixAdenovirus inf. (Ph.III)

Elvitegravir+cobicistat+emtricitabine+tenofovir GileadHIV/AIDS (Ph.III)

Sofosbuvir+GS-5816 GileadHCV inf. (Ph.III)

Tenofovir alafenamide GileadHBV inf. (Ph.III)

GSK 1437173A GSKHerpes (Ph.III)

Cobicistat+darunavir J&JHIV/AIDS (Pre-reg.)

Actoxumab/bezlotoxumab/ MK-3415A MerckClost. diff. inf. (Ph.III)

Letermovir/MK-8228 MerckCMV prophylaxis (Ph.III)

MK-5172A MerckHepatitis C (Ph.III)

VZV vaccine/V212 MerckHerpes zoster (Ph.III)

V419 MerckPediatric hexavalent vax (Ph.III)

V503 MerckHPV-related cancers (Pre-reg.)

Deltyba OtsukaTuberculosis (Ph.III)

PF-05212366 PfizerMeningitis B vax (Ph.III)

Clostridium difficile SanofiToxoid vaccine (Ph.III)

PR5i SanofiDTP-HebB-Polio-Hib (Pre-reg.)

Quadracel SanofiDip-tet-pertusis-polio (Ph.III)


Zmapp Mapp BiopharmaceuticalIndication: Ebola virus infections (clinical)What the analysts are saying: There is strong interest in ZMapp glob-ally, particularly in the African countries where the Ebola epidemic has been occurring. As of early November, there were 13,000 cases and almost 5,000 deaths—making it the largest and most deadly since the disease was discovered in the ’70s—but the CDC estimates that totals could top 500,000 early in 2015. ZMapp was in animal testing, but the Ebola epidemic has spurred tremendous interest and urgency. Even so, only a few hundred doses may be available by the end of 2014. Current formulation of ZMapp involves a cocktail of three monoclonal antibodies, which requires three manufacturing processes; this makes the production complex and requires many partnerships for the small San Diego-based company behind the product, Mapp Biopharmaceutical. There have been no formal studies of ZMapp conducted in humans. A small number of Ebola patients have been given ZMapp on a compassionate-use basis, but the impact of the product on these patients is unclear. Human trials of ZMapp may also face challenges from patients, healthcare professionals and govern-ments who object ethically/morally to using the standard “placebo-controlled study” design in Ebola patients (given the high mortality rate of the disease). —Michael D’Aust Garcia, SVP, GfK Health


Opdivo (nivolumab) Bristol-Myers SquibbIndication: 2L NSCLC (Pre-reg.); 1L NSCLC/head + neck/mela-noma/RCC (Ph. III)What the clinical trials found: Ph.III CHECKMATE 037 trial showed slightly more than 20% increase in response rate in mela-noma patients previously treated with BMS’s Yervoy. The ‘063 Ph.II 2L/3L lung trial showed ORR of 15% with one-year survival of 41%. AEs were in line with previous trials.Credit Suisse Success Probability and inThought Comment: 65%. Opdivo is very similar to Merck’s anti-PD1 compound, the recently launched Keytruda (pembrolizumab). There’s a lot of talk about which one of them is better; we don’t know the answer to that yet. Merck did a great job of getting its drug on the market first and it will benefit from that. But it will be interesting to see how the labels compare, as there’s potential for Opdivo to work more broadly. In 2015 we will learn a lot very quickly about just how important these drugs are going to be. Expected launch: 1Q 2015 (Source: Credit Suisse)Credit Suisse revenue forecast: $11.9B in global annual sales by 2020What the analysts are saying: Based on this very early stage data, it appears that all the different IO agents (Roche’s PD-L1 MPD-L3280A, AZ’s PD-L1 MEDI4736, Merck’s PD-1 Keytruda) have similar activities in these respective indications. For lung, response rates for all the different drugs that have been tested so far is around 20%, and they are all relatively well-tolerated, but have slightly dif-ferent toxicity profiles. So it will be interesting to see how doctors decide to choose these different agents, especially in their current indications as monotherapy. —Arnold DuBell , PhD, consultant, Kantar Health

Palbociclib PfizerIndication: ER+ breast cancer (Pre-reg.); NSCLC (Ph. II/III)What the clinical trials found: Phase II PALOMA-1 showed that patients who were given palbociclib and letrozole experienced a significantly longer PFS period (20.2 mos.) vs. patients who received letrozole alone (10.2 mos.). The combination was gener-ally well-tolerated.Credit Suisse Success Probability and inThought Comment: 80%. This Breakthrough Therapy and Priority Review cancer drug, which has a PDUFA date of April 13, 2015, could be critical to Pfizer’s oncology ambitions. It’s ahead of, but could compete with, CDK4/6 inhibitors from Novartis (LEE011) and Lilly (abemaciclib), both in Ph.III. Expected launch: 2015 (Source: Credit Suisse)Credit Suisse revenue forecast: $3.2B in global annual sales by 2020What the analysts are saying: This once-daily, small-molecule CDK4/6 inhibitor had phenomenal efficacy in terms of PFS ben-efit and as a result will be very well-received. The only question

OncologyVeliparib AbbVieBreast/NSCLC (Ph.III)

ABT-199 AbbVieAML/CLL (Ph.II)

Trebananib AmgenOvarian (Ph.III)

Rilotumumab AmgenGastric (Ph.III), NSCLC (Ph. II/III)

T-VEC AmgenMal. mel. (Pre-reg.)

AZD9292 AstraZenecaNSCLC (Ph.III)

MEDI4736 AstraZenecaNSCLC (Ph.III)

Moxetumomab AstraZenecaLeukemia (Ph.III)

Olaparib AstraZenecaOvarian (Pre-reg.) gastric/breast (Ph.III)

Selumetanib AstraZenecaNSCLC/thyroid. mel.(Ph.III)

Tremelimumab AstraZenecaMesothelioma (Ph.III)

Elotuzumab BMS/AbbVieMultiple myeloma (Ph.III)

Abemaciclib Eli LillyBreast (Ph.III)

Necitumumab Eli LillyNSCLC (Ph.III)

Idelalisib GileadCLL/NHL (Ph.III)

Momelotinib GileadMyelofibrosis (Ph.III)

ARN-509 J&JProstate (Ph. III)

Daratumumab J&JMult. myeloma (Ph.III)

Yondelis J&JBreast/sarcoma/ovarian (Ph.III)

LBH589 NovartisMult. myeloma (Pre-reg.)

LDE225 NovartisBCC (Pre-reg.)

BKM120 NovartisBreast (Ph.III)

PKC412 NovartisAML (Ph.III)

LEE011 NovartisBreast (Ph.III)

LGX818 NovartisMal. mel. (Ph.III)

TKI258 NovartisSolid tumors (Ph.III)

S-1 OtsukaPancreatic (Ph.III)

Sativex OtsukaCancer pain (Ph.III)

Inotuzumab PfizerALL (Ph.III)

Alectinib RocheNSCLC (Ph. III)

Cobimetinib combo RocheMet. mel. (Ph.III)

MPDL3280A/ RG7446 RocheNSCLC (Ph. III)

Custirsen TevaProstate (Ph.III)

Lipegfilgrastim TevaNHL (Ph.III)




that doctors will have is that the Ph.II data did not show signifi-cant advantage in OS. I do not think doctors will hold that against palbo’, given that this was a Ph.II trial and the PFS benefit was so significant and so clinically relevant. It will be approved by FDA in April. —Arnold DuBell , PhD, consultant, Kantar Health



Bosatria (mepolizumab) GlaxoSmithKlineIndication: Asthma (Pre-reg.)What the clinical trials found: Reductions in clinically significant exacerbations of asthma vs. placebo were 47% lower for IV mepo-lizumab and 53% lower for SC mepolizumab (MENSA, Ph.III). Patients with severe eosinophilic asthma who received mepolizumab 100mg SC once a month achieved greater reductions in maintenance oral corticosteroid dose, during weeks 20-24, compared with patients on placebo, while maintaining asthma control (SIRIUS, Ph.III). Credit Suisse Success Probability: 70%. Expected launch: 2016 (Source: Credit Suisse)Credit Suisse revenue forecast: $570 million in annual global sales by 2020What the analysts are saying: Mepolizumab, an interleukin (IL)-5 biologic, offers an attractive proposition for maintenance treatment for patients with severe eosinophilic asthma, identified by a blood eosinophil count. The first challenge will be ensuring that severe asthma patients obtain this reading, making them candidates for treatment. Mepolizumab will also face some competition from Teva and AstraZeneca, meaning it is a race to clearly carve out a new niche as the choice of IL-5 within the treatment community. —Alex Bastian, VP, GfK Market Access (Health)

Ultibro (indacaterol/glycopyrrolate) NovartisIndication: COPD (Ph.III)What the clinical trials found: Ultibro met the primary endpoint, demonstrating non-inferiority of the Ultibro Breezhaler vs. tiotropium + formoterol in improving health-related quality of life outcomes, as well as the secondary endpoint, demonstrating superiority vs. tiotropium + formoterol by improving lung function (QUANTIFY, Ph.III). Once-daily glycopyrrolate/indacaterol was associated with a 31% reduction in the rate of moderate-to-severe exacerbations, compared with twice daily salmeterol/fluticasone (LANTERN, Ph.III).Credit Suisse Success Probability: 60%. Expected launch: 2016 (Source: Credit Suisse)Credit Suisse revenue forecast: $1.5 billion in annual global sales by 2020What the analysts are saying: Market access will be important for Ultibro. Clinical trials demonstrating superiority over the standard of care comprise a strong market-access lever in pricing and reim-bursement negotiations. However, a variety of cheaper alternatives threaten to make this market more sensitive to price and access. Most payers and pulmonologists across the EU5 are open to prescribing generic versions of Seretide (GSK), Symbicort (AZ) and Spiriva (BI) when they launch. Being the first steroid-free dual brochodila-tor will be useful for treating physicians. However, the importance of updates to guidelines and the change in clinical practice will be key for Ultibro. —Alex Bastian, VP, GfK Market Access (Health)

RespiratoryMasitinib AB ScienceAsthma (Ph.III)

Selexipag ActelionPAH (Ph.III)

Benralizumab AstraZenecaAsthma/COPD (Ph.III)

Brodalumab AstraZenecaSevere asthma (Ph.III)

PT003 GFF AstraZenecaCOPD (Ph.III)

PT001 GP AstraZenecaCOPD (Ph.III)

Olodaterol+tiotropium bromide Boehringer IngelheimCOPD (Pre-reg.)

Aclidinium bromide+formoterol fumarate ForestCOPD (Ph.III)

Ragweed immunotherapy GreerAllergic rhinitis (Ph.III)

Fluticasone furoate+ umeclidinium+vilanterol GSKCOPD (Ph.III)

Vilanterol GSKCOPD (Ph.III)

Esuberaprost LungRxPAH (Ph.III)

MK-8237 MerckAllergy (Ph.III)

Formoterol+glycopyrrolate NektarCOPD (Ph.III)

Inhaled glycopyrrolate NovartisAsthma/COPD (Ph.III)

Glycopyrrolate+indacaterol NovartisCOPD (Ph.III)

Reslizumab TevaAsthma (Ph.III)


Lebrikizumab RocheIndication: Asthma (Ph.III)What the clinical trials found: Asthma attacks were reduced by 60% in patients in Ph.IIb with a high level of the biomarker periostin, compared with 5% in patients with a low level of periostin (LUTE, VERSE). A 9.1% increase in FEV1 over placebo was seen at 12 weeks in the pooled periostin-high treatment arms, vs. a 2.6% increase over placebo in the periostin-low arms. No clinically important safety signals reported.Credit Suisse Success Probability: 50%. Expected launch: 2018 (Source: Credit Suisse)Credit Suisse revenue forecast: $308 million in annual global sales by 2020What the analysts are saying: A key driver of uptake—and payer coverage—will be the degree to which lebrikizumab reduces exac-erbations or the oral corticosteroid dose that severe asthmatics require. This drug also faces the challenges of being a new per-sonalized medicine option in asthma—and the hurdles that come along with shifting the mindset in the diagnosis and treatment of asthma. Obtaining coverage and ease of ordering the associated test will be critical for lebrikizumab. —Alex Bastian, VP, GfK Market Access (Health)


PIPELINE 2015 UEROSTO COMMODO ODIONUL 2010



NEUROLOGYMK-8931 MerckIndication: Alzheimer’s disease (Ph.III)What the clinical trials found: Treatment with oral MK 8931 in a Ph.-I trial of 32 patients with Alzheimer’s significantly and dose-dependently lowered CSF beta amyloid levels. The average reduc-tion, at the highest dosage, was more than 80% from baseline. It was generally well-tolerated.Credit Suisse Success Probability and inThought Comment: 20%. There’s been three major approaches taken to plaque-busting in Alzheimer’s: 1) trying to prevent the deposition of plaque, or remove it, from the brain, which the anti-Aβ monoclonal antibodies bapineu-zumab and solanezumab (still being developed though they didn’t work on the first go-round) tried to do; 2) trying to prevent formation of the ingredients of the plaque; and 3) the BACE1 inhibitors like MK-8931 that are also trying to prevent formation of the amyloid beta. It’s going to be years before we find out the answer to these BACE inhibitors. They must be tested in very large, long trials in people who are not very sick to begin with. But coming up with something that could slow or halt the progression of AD is still a primary goal in drug development today. We have talked to many experts about the BACE inhibitor, and they all give it about a 50-50 shot. But if it works, it’s going to be huge. Expected launch: 2018 (Source: Credit Suisse) Credit Suisse revenue forecast: $2.3 billion in global annual sales by 2020What the physicians are saying: Early thoughts by neurologists indicate tempered enthusiasm for the class. Neurologists are excited about a potentially new method of treating and slowing Alzheimer’s disease, feeling that it shows great promise. However, with trials ongoing for MK-8931 and the recent failed attempts of other pipeline agents, neurologists are taking a “wait and see” approach before getting too excited. —Paul Wojciak, research director, lead, GfK Therapeutic Class Dynamics syndicated product line

ORPHANSebelipase alfa Synageva BioPharmaIndication: Wolman disease (Pre-reg.) What the clinical trials found: Sebelipase alfa improved markers of liver injury, dyslipidemia and liver fat content—key indicators related to Wolman disease. The Ph. III ARISE trial met its primary endpoint, with 31% (11/36) of patients reaching normal levels of ALT, the study’s primary endpoint and one of the markers of liver injury, vs. 7% on placebo. The relative reduction in LDL and non-LDL cholesterol was 28%, vs. 6% to 7% among those in the placebo group. Most AEs were mild and unrelated to sebelipase alfa.What the analysts are saying: This recombinant human lysosomal acid lipase is being developed as an enzyme replacement therapy to treat lysosomal acid lipase (LAL) deficiency, also known as Wolman

Other METABOLIC

Velcacetide/AMG-416 AmgenSecondary hyperparathyroidism (Ph.III)

Tofogliflozin GenentechType 2 diabetes (Ph.III)

Eperzan (albiglutide) GSKType 2 diabetes (Pre-reg.)

Basal insulin peglispro Eli LillyT1/2 diabetes (Ph.III)

Insulin glargine biosimilar Eli LillyT2 diabetes (Pre-reg.)

Ertugliflozin/MK-8835 MerckType 2 diabetes (Ph.III)

Omarigliptin/MK-3102 MerckType 2 diabetes (Ph.III)

Insulin glargine biosim/MK-1293 MerckT1/2 diabetes (Ph.III)

Ryzodeg Novo NordiskT1/2 diabetes (Pre-reg.)

Tresiba Novo NordiskType 2 diabetes (Pre-reg.)

Xultophy (IDegLira) Novo NordiskType 2 diabetes (Ph.III)

NN1218 Novo NordiskT1/2 diabetes (Ph.III)

Semaglutide Novo NordiskType 2 diabetes (Ph.III)

Ertugliflozin PfizerType 2 diabetes (Ph.III)

LixiLan SanofiT2 diabetes (Ph.III)

Lyxumia (lixisenatide) SanofiT2 diabetes (Ph.III)

Toujeo (U300) SanofiT1/2 diabetes (Pre-reg.)

NEUROLOGY

Duopa AbbVieParkinson’s dis. (Pre-reg.)

Solanezumab Eli LillyAlzheimer’s (Ph.III)

Tanezumab Eli LillyPain (Ph.III)

LU AE58054 LundbeckAlzheimer’s (Ph.III)

Suggamadex MerckNeuromuscular blockade (Pre-reg.)

Brexpiprazole OtsukaSchizophrenia/MDD (Pre-reg.)

Bitopertin RocheSchizophrenia (Ph.III)

Gantenerumab RocheAlzheimer’s (Ph.III)

SHP 465 ShireADHD (Pre-reg.)

ORPHAN

Miglustat ActelionNiemann-Pick dis. (Pre-reg.)

Migalastat AmicusFabry’s disease (Ph.III)

Lumacaftor/ivacaftor VertexCF (Pre-reg.)

N8-GP Novo NordiskHemophilia A (Ph.III)

N9-GP Novo NordiskHemophilia B (Ph.III)

WOMEN’S HEALTH

Elagolix AbbVieEndometriosis (Ph.III)

MK-8962 MerckFertility (Pre-reg.)

Menerba United BiotechVasomotor sympt. (Ph.III)


disease. Citigroup indicated three concerns surrounding sebelipase alfa’s commercial chances. The analyst noted that the “key” questions include, “1) prevalence estimates of LAL deficiency are variable, 2) identification of patients could be challenging as many of the signs and symptoms of LAL deficiency overlap with other conditions, 3) LAL deficiency patients have a range of disease severity and it’s unclear which patients would require treatment.” These concerns could “result in a slower than expected launch compared to other orphan drug peers.” Also, concerns over the pain profile of the product could impact uptake. —Susan Garfield, SVP, GfK Health – Market Access

Documents

PIPELINE REPORT 2015 - media.mmm-online.commedia.mmm-online.com/documents/97/41r1_mmm_dec14_24005.pdf · Results of Merck’s IMPROVE-IT ... THE PIPELINE REPORT 2015 These 16 sprouts,